Sleep Deprivation Aggravates Periodontitis Through Trigeminal-Periodontal Neuroimmune Pathway

Continuous sleep deprivation (SD) induces a systemic "inflammatory storm" and immune dysregulation, yet the specific impact it exerts on periodontitis and the corresponding therapeutic interventions for it remain unclear. Consequently, this study elucidates the neuroimmune mechanisms through which SD influences ligature-induced periodontitis (LIP) and introduces an adjunctive therapeutic method – electroacupuncture (EA) . Approved by the Ethics Committee, a LIP+SD and EA intervention model was established using 6-8 weeks of female C57BL/6. Then, screening experiments (ELISA, public databases, flow cytometry, immunofluorescence, etc.) have revealed that acetylcholine (ACh), α7 nicotinic acetylcholine receptor (α7nAChR), and acetylcholinesterase (AChE) play a pivotal role in the exacerbation of periodontitis by SD with a decrease in ACh levels, downregulation of α7nAChR on macrophages, and an increase in trigeminal ganglion-derived AChE. Ultimately, both in vivo and in vitro experiments demonstrated that EA inhibits M1 polarization of macrophages and promotes M2 polarization by activating the α7nAChR. Therefore, SD aggravates periodontitis through the trigeminal-periodontal neuroimmune pathway, which is mediated by the AChE-ACh-α7nAChR axis, whereas EA reverses this pathological process to some extent by activating α7nAChR on macrophages. These results offer new insights into the role of the "oral-brain axis" in the progression of oral diseases and provide novel clues for adjunctive therapy in patients with periodontitis complicated by sleep disorders.